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• W1976994047 abstract "Daphnane-type diterpene gnidimacrin isolated from the Chinese plant Stellera chamaejasme L. is an antitumor agent that activates protein kinase C (PKC). The mechanism of antitumor action of gnidimacrin and the possible involvement of PKC were examined using sensitive K562 and refractory HLE cells. Gnidimacrin did bind to K562 cells 3 times more than to HLE cells. Immunoblot analyses revealed pronounced PKC betaII expression in gnidimacrin sensitive cell lines including K562 cells, while refractory HLE cells strongly expressed PKC alpha, but not PKC betaII. In a 24-hr exposure of K562 cells to gnidimacrin, G1 phase arrest and inhibition of cdk2 kinase activity was found at growth-inhibitory concentration (0.0005 microg/ml). Complete inhibition of cdk2 activity and maximum G1 phase arrest were observed at 0.005 microg/ml, however, these biological effects were reduced at 0.05 microg/ml (260 times the 50% inhibitory concentration). Cellular PKC after a 24-hr exposure was examined by immunoblot analysis and specific binding of [3H]phorbol-12,13-dibutyrate as a ligand of PKC. Expression and the amount of functional PKC of K562 cells were not changed at 0.002 microg/ml, but down-regulated to less than 1/10th of the control at 0.05 microg/ml. The reduction of biological effects at 0.05 microg/ml is most likely due to PKC down-regulation. Our results suggest that PKC (particularly betaII) is one of the major determinants of the ability of cells to respond to gnidimacrin and that the antitumor action might be associated with cell-cycle regulation through suppression of cdk2 activity." @default.
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• W1976994047 date "1998-07-17" @default.
• W1976994047 modified "2023-10-18" @default.
• W1976994047 title "Mechanism of antitumor action of PKC activator, gnidimacrin" @default.
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• W1976994047 doi "https://doi.org/10.1002/(sici)1097-0215(19980717)77:2<243::aid-ijc13>3.0.co;2-c" @default.
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